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Protein

MAP/microtubule affinity-regulating kinase 3

Gene

Mark3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase. Involved in the specific phosphorylation of microtubule-associated proteins for MAPT/TAU, MAP2 and MAP4. Phosphorylates CDC25C. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei85ATPPROSITE-ProRule annotation1
Active sitei178Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi62 – 70ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • negative regulation of hippo signaling Source: UniProtKB
  • peptidyl-serine autophosphorylation Source: ARUK-UCL
  • peptidyl-serine phosphorylation Source: ARUK-UCL
  • positive regulation of protein binding Source: ARUK-UCL
  • protein phosphorylation Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5673000 RAF activation
R-MMU-5674135 MAP2K and MAPK activation
R-MMU-5675221 Negative regulation of MAPK pathway

Names & Taxonomyi

Protein namesi
Recommended name:
MAP/microtubule affinity-regulating kinase 3 (EC:2.7.11.1)
Alternative name(s):
ELKL motif kinase 2
Short name:
EMK-2
MPK-10
Gene namesi
Name:Mark3
Synonyms:Emk2, Mpk10
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1341865 Mark3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863051 – 753MAP/microtubule affinity-regulating kinase 3Add BLAST753

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphoserineBy similarity1
Modified residuei211Phosphothreonine; by LKB1By similarity1
Modified residuei368PhosphoserineCombined sources1
Modified residuei374PhosphoserineCombined sources1
Modified residuei376PhosphoserineBy similarity1
Modified residuei380PhosphoserineCombined sources1
Modified residuei383PhosphoserineCombined sources1
Modified residuei400PhosphoserineCombined sources1
Modified residuei419PhosphoserineCombined sources1
Modified residuei469PhosphoserineBy similarity1
Modified residuei540PhosphoserineCombined sources1
Modified residuei543PhosphoserineCombined sources1
Modified residuei549PhosphothreonineCombined sources1
Modified residuei564Phosphothreonine; by PKC/PRKCZBy similarity1
Modified residuei583PhosphoserineBy similarity1
Modified residuei598PhosphoserineBy similarity1
Modified residuei601PhosphoserineBy similarity1
Modified residuei643PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ03141
PaxDbiQ03141
PeptideAtlasiQ03141
PRIDEiQ03141

PTM databases

iPTMnetiQ03141
PhosphoSitePlusiQ03141

Expressioni

Gene expression databases

BgeeiENSMUSG00000007411
CleanExiMM_MARK3
ExpressionAtlasiQ03141 baseline and differential
GenevisibleiQ03141 MM

Interactioni

Subunit structurei

Interacts with MAPT/TAU. Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5.By similarity

Protein-protein interaction databases

BioGridi201312, 6 interactors
IntActiQ03141, 1 interactor
STRINGi10090.ENSMUSP00000082017

Structurei

Secondary structure

1753
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi672 – 685Combined sources14
Beta strandi689 – 692Combined sources4
Beta strandi698 – 702Combined sources5
Beta strandi704 – 706Combined sources3
Helixi707 – 709Combined sources3
Beta strandi711 – 719Combined sources9
Beta strandi721 – 735Combined sources15
Helixi737 – 750Combined sources14

3D structure databases

ProteinModelPortaliQ03141
SMRiQ03141
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ03141

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 307Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini326 – 365UBAPROSITE-ProRule annotationAdd BLAST40
Domaini695 – 744KA1PROSITE-ProRule annotationAdd BLAST50

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi374 – 412Ser-richAdd BLAST39

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0586 Eukaryota
ENOG410XNQ0 LUCA
GeneTreeiENSGT00900000140806
HOGENOMiHOG000233025
HOVERGENiHBG052453
InParanoidiQ03141
KOiK08798
OMAiRWINAGF
OrthoDBiEOG091G0D1E
PhylomeDBiQ03141
TreeFamiTF315213

Family and domain databases

InterProiView protein in InterPro
IPR028375 KA1/Ssp2_C
IPR001772 KA1_dom
IPR011009 Kinase-like_dom_sf
IPR033624 MARK/par1
IPR033628 MARK3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
PANTHERiPTHR24346 PTHR24346, 1 hit
PTHR24346:SF1 PTHR24346:SF1, 1 hit
PfamiView protein in Pfam
PF02149 KA1, 1 hit
PF00069 Pkinase, 1 hit
PF00627 UBA, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00165 UBA, 1 hit
SUPFAMiSSF103243 SSF103243, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50032 KA1, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50030 UBA, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q03141-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTRTPLPTV NERDTENHIS HGDGRQEVTS RTGRSGARCR NSIASCADEQ
60 70 80 90 100
PHIGNYRLLK TIGKGNFAKV KLARHILTGR EVAIKIIDKT QLNPTSLQKL
110 120 130 140 150
FREVRIMKIL NHPNIVKLFE VIETEKTLYL IMEYASGGEV FDYLVAHGRM
160 170 180 190 200
KEKEARAKFR QIVSAVQYCH QKRIVHRDLK AENLLLDADM NIKIADFGFS
210 220 230 240 250
NEFTVGSKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG VILYTLVSGS
260 270 280 290 300
LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPVKRGTLEQ
310 320 330 340 350
IMKDRWINAG HEEDELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS
360 370 380 390 400
KMKYDEITAT YLLLGRKSAE LDASDSSSSS NLSLAKVRPN SDLSNSTGQS
410 420 430 440 450
PHHKGQRSVS SSQKQRRYSD HAGPAIPSVV AYPKRSQTST ADSDLKEDGI
460 470 480 490 500
PSRKSSSSAV GGKGIAPASP MLGNAGNPNK ADIPERKKSP AVPSSNTASG
510 520 530 540 550
GMTRRNTYVC SERCAADRHS VIQNGKENSA IPDERTPVAS THSISSATTP
560 570 580 590 600
DRIRFPRGTA SRSTFHGQPR ERRTATYNGP PASPSLSHEA TPLSQTRSRG
610 620 630 640 650
STNLFSKLTS KLTRRNMSFR FIKRLPTEYE RNGRYEGSSR NVSSEQKDEN
660 670 680 690 700
REAKPRSLRF TWSMKTTSSM DPSDMMREIR KVLDANNCDY EQRERFLLFC
710 720 730 740 750
VHGDGHAENL VQWEMEVCKL PRLSLNGVRF KRISGTSIAF KNIASKIANE

LKL
Length:753
Mass (Da):84,390
Last modified:November 8, 2005 - v2
Checksum:iB597BDD0398617CF
GO
Isoform 2 (identifier: Q03141-2) [UniParc]FASTAAdd to basket
Also known as: ELKL motif kinase 2 short form

The sequence of this isoform differs from the canonical sequence as follows:
     615-638: Missing.

Show »
Length:729
Mass (Da):81,400
Checksum:iD76FBB9A27ED19C9
GO
Isoform 3 (identifier: Q03141-3) [UniParc]FASTAAdd to basket
Also known as: ELKL motif kinase 2 long form

The sequence of this isoform differs from the canonical sequence as follows:
     615-623: Missing.

Show »
Length:744
Mass (Da):83,209
Checksum:i2CCA8FA8AEE20360
GO

Sequence cautioni

The sequence AAH26445 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC35922 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti333D → V in BAC35922 (PubMed:16141072).Curated1
Sequence conflicti496N → S in AAF64456 (Ref. 1) Curated1
Sequence conflicti511S → G in BAC35922 (PubMed:16141072).Curated1
Sequence conflicti684D → G in BAC35922 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016140615 – 638Missing in isoform 2. 3 PublicationsAdd BLAST24
Alternative sequenceiVSP_016141615 – 623Missing in isoform 3. 2 Publications9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240783 mRNA Translation: AAF64456.1
AK075742 mRNA Translation: BAC35922.1 Different initiation.
AK132247 mRNA Translation: BAE21056.1
AK166157 mRNA Translation: BAE38602.1
BC026445 mRNA Translation: AAH26445.1 Different initiation.
X57244 mRNA Translation: CAA40520.1
CCDSiCCDS26181.1 [Q03141-3]
CCDS26182.1 [Q03141-2]
PIRiS30496
RefSeqiNP_067491.2, NM_021516.4 [Q03141-3]
NP_073712.2, NM_022801.4 [Q03141-2]
XP_006515578.1, XM_006515515.3 [Q03141-1]
UniGeneiMm.260504
Mm.420865

Genome annotation databases

EnsembliENSMUST00000075281; ENSMUSP00000074757; ENSMUSG00000007411 [Q03141-2]
ENSMUST00000084953; ENSMUSP00000082017; ENSMUSG00000007411 [Q03141-3]
ENSMUST00000221459; ENSMUSP00000152483; ENSMUSG00000007411 [Q03141-1]
GeneIDi17169
KEGGimmu:17169
UCSCiuc007pdk.2 mouse [Q03141-3]
uc007pdl.2 mouse [Q03141-2]
uc007pdm.2 mouse [Q03141-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMARK3_MOUSE
AccessioniPrimary (citable) accession number: Q03141
Secondary accession number(s): Q3TM40
, Q3V1U3, Q8C6G9, Q8R375, Q9JKE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 8, 2005
Last modified: July 18, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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